The metabolism of hemoglobin and its heme moiety are under investigation. In particular, we are studying the function of serum proteins in the transport and catabolism of heme and heme precursors. Hemopexin, a serum Beta-glycoprotein, functions in the selective transport of intravascular heme to the liver parenchymal cell and thus plays a role in conserving biologically available iron as well as in preventing toxic effects of heme. Many characteristics of the hemopexin molecule are known, but important properties remain to be explored. What are the mechanisms of the binding of the hemopexin-heme complex to the liver cell and of the release from it? What portions of the hemopexin molecule are responsible for the heme-hemopexin formation, the interaction with the hepatocyte membrane and the antibody binding? What is the function of hemopexin in myoglobin metabolism? And how is the synthesis of this protein regulated? We plan to study hemopexin's function in heme metabolism at several levels. First, we will continue to assess the clinical diagnostic usefulness of serum hemopexin levels and to investigate the metabolism of hemopexin in disease states in which the metabolism of myoglobin, hemoglobin or heme is altered. Second, we will continue to define the physical-chemical characteristics of the hemopexin molecule and its interaction with heme to provide basic information required to understand how this protein functions in heme transport. In particular, we will characterize the kinetics of the heme-hemopexin binding reaction and initiate a study of the primary structure of the protein. Third, we will study the regulation of hemopexin synthesis, especially the effect of heme and its precursors.